Metabolic syndrome, obesity, and gastrointestinal cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Fujihara S
PROVIDER: S-EPMC3530232 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Metabolic syndrome, obesity, and gastrointestinal cancer.
Fujihara Shintaro S Mori Hirohito H Kobara Hideki H Nishiyama Noriko N Kobayashi Mitsuyoshi M Oryu Makoto M Masaki Tsutomu T
Gastroenterology research and practice 20121211
METABOLIC SYNDROME IS A CLUSTER OF METABOLIC ABNORMALITIES AND IS DEFINED AS THE PRESENCE OF THREE OR MORE OF THE FOLLOWING FACTORS: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. Obesity, which is accompanied by metabolic dysregulation often manifested in the metabolic syndrome, is an established risk factor for many cancers. Adipose tissue, particularly visceral fat, is an important metabolic tissu ...[more]
Similar Datasets
Project description:ObjectivesThe metabolic dysfunction driven by obesity, including hyperglycemia and dyslipidemia, increases risk for developing at least 13 cancer types. The concept of "metabolic dysfunction" is often defined by meeting various combinations of criteria for metabolic syndrome. However, the lack of a unified definition of metabolic dysfunction makes it difficult to compare findings across studies. This review summarizes 129 studies that evaluated variable definitions of metabolic dysfunction in relation to obesity-related cancer risk and mortality after a cancer diagnosis. Strategies for metabolic dysfunction management are also discussed.MethodsA comprehensive search of relevant publications in MEDLINE (PubMed) and Google Scholar with review of references was conducted.ResultsMetabolic dysfunction, defined as metabolic syndrome diagnosis or any number of metabolic syndrome criteria out of clinical range, inflammatory biomarkers, or markers of metabolic organ function, has been associated with risk for, and mortality from, colorectal, pancreatic, postmenopausal breast, and bladder cancers. Metabolic dysfunction associations with breast and colorectal cancer risk have been observed independently of BMI, with increased risk in individuals with metabolically unhealthy normal weight or overweight/obesity compared with metabolically healthy normal weight.ConclusionMetabolic dysfunction is a key risk factor for obesity-related cancer, regardless of obesity status. Nonetheless, a harmonized definition of metabolic dysfunction will further clarify the magnitude of the relationship across cancer types, enable better comparisons across studies, and further guide criteria for obesity-related cancer risk stratification.
| S-EPMC9302704 | biostudies-literature
Project description:There is a fine balance in the mutual relationship between the intestinal microbiota and its mammalian host. It is thought that disruptions in this fine balance contribute/account for the pathogenesis of many diseases. Recently, the significance of the relationship between gut microbiota and its mammalian host in the pathogenesis of obesity and the metabolic syndrome has been demonstrated. Emerging data has linked intestinal dysbiosis to several gastrointestinal diseases including inflammatory bowel disease, irritable bowel syndrome, nonalcoholic fatty liver disease, and gastrointestinal malignancy. This article is intended to review the role of gut microbiota maintenance/alterations of gut microbiota as a significant factor as a significant factor discriminating between health and common diseases. Based on current available data, the role of microbial manipulation in disease management remains to be further defined and a focus for further clinical investigation.
| S-EPMC4816244 | biostudies-other
Project description:Obesity contributes to an estimated forty-percent, or 630,000 cases, of malignant neoplasms diagnosed in the United States[1] and higher body mass index (BMI) has been associated with at least seventeen types of solid tumors, including 9% of all breast cancer cases. In this review, we discuss the impact of obesity and consequences of obesity, including the metabolic syndrome and type 2 diabetes mellitus, on breast cancer risk and recurrence. Recent work has identified multiple molecular mechanisms that may underlie the association between obesity and breast cancer. In particular, insulin resistance, increased inflammatory cytokines, leptin signaling, and adipokine signaling have been shown to affect breast cancer risk and outcomes. While obesity is associated with higher breast cancer incidences and worse breast cancer outcomes, several risk reduction methods have been shown to attenuate these risks. Both metformin and statins have been shown to improve disease free survival and overall survival compared to non-users. Metformin also has been associated with lower risk of breast cancer incidence. Furthermore, increased physical activity and weight loss have been shown to decrease risk of breast cancer, especially in post-menopausal women. These studies have emphasized the potential impact that lifestyle changes can have on breast cancer risk and outcomes, and demonstrate the need for randomized control trials to evaluate the roles of metformin and statins for the treatment and chemoprevention of breast cancer.
| S-EPMC6619425 | biostudies-literature
Project description:The G-protein beta subunit 3 (GNB3) gene has been implicated in obesity risk; however, the molecular mechanism of GNB3-related disease is unknown. GNB3 duplication is responsible for a syndromic form of childhood obesity, and an activating DNA sequence variant (C825T) in GNB3 is also associated with obesity. To test the hypothesis that GNB3 overexpression causes obesity, we created bacterial artificial chromosome (BAC) transgenic mice that carry an extra copy of the human GNB3 risk allele. Here we show that GNB3-T/+ mice have increased adiposity, but not greater food intake or a defect in satiety. GNB3-T/+ mice have elevated fasting plasma glucose, insulin, and C-peptide, as well as glucose intolerance, indicating type 2 diabetes. Fasting plasma leptin, triglycerides, cholesterol and phospholipids are elevated, suggesting metabolic syndrome. Based on a battery of behavioral tests, GNB3-T/+ mice did not exhibit anxiety- or depressive-like phenotypes. GNB3-T/+ and wild-type animals have similar activity levels and heat production; however, GNB3-T/+ mice exhibit dysregulation of acute thermogenesis. Finally, Ucp1 expression is significantly lower in white adipose tissue (WAT) in GNB3-T/+ mice, suggestive of WAT remodeling that could lead to impaired cellular thermogenesis. Taken together, our study provides the first functional link between GNB3 and obesity, and presents insight into novel pathways that could be applied to combat obesity and type 2 diabetes.
| S-EPMC5716578 | biostudies-literature
Project description:Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.
| S-EPMC7432525 | biostudies-literature
Project description:Dragonflies infected with noninvasive gregarine gut parasites (Apicomplexa: Eugregarinorida) [corrected] have reduced flight-muscle performance, an inability to metabolize lipid in their muscles, twofold-elevated hemolymph carbohydrate concentrations, and they accumulate fat in their thorax in a manner analogous to mammalian obesity. Gregarine infection is associated with inappropriate responses of hemolymph carbohydrate concentration to insulin and with chronic activation in the flight muscles of p38 MAP kinase, a signaling molecule involved in immune and stress responses. Short-term exposure to gregarine excretory/secretory products caused elevated blood carbohydrate and p38 MAPK activation in healthy individuals. These characteristics comprise a set of symptoms and processes that are known in mammals as metabolic syndrome but which have not previously been described in other animal taxa. In addition to expanding the known taxonomic breadth of metabolic disease, these results indicate that insects may be useful experimental models for studying its underlying biology and mechanisms.
| S-EPMC1693743 | biostudies-literature
Project description:Bile acids are increasingly recognized as key regulators of systemic metabolism. While bile acids have long been known to play important and direct roles in nutrient absorption, bile acids also serve as signalling molecules. Bile acid interactions with the nuclear hormone receptor farnesoid X receptor (FXR) and the membrane receptor G-protein-coupled bile acid receptor 5 (TGR5) can regulate incretin hormone and fibroblast growth factor 19 (FGF19) secretion, cholesterol metabolism, and systemic energy expenditure. Bile acid levels and distribution are altered in type 2 diabetes and increased following bariatric procedures, in parallel with reduced body weight and improved insulin sensitivity and glycaemic control. Thus, modulation of bile acid levels and signalling, using bile acid binding resins, TGR5 agonists, and FXR agonists, may serve as a potent therapeutic approach for the treatment of obesity, type 2 diabetes, and other components of the metabolic syndrome in humans.
| S-EPMC4159616 | biostudies-literature
Project description:ObjectiveThis study investigated the associations between obesity, metabolic syndrome (MetS), the combination of these two components as a metabolic obesity phenotype, and endometrial cancer risk in East Asian women.MethodsA total of 6,097,686 cancer-free women aged 40-74 years who underwent the National Health Insurance Service health examination between 2009 and 2010 were included. Cancer incidence was identified using the healthcare utilization database. Associations between baseline obesity (body mass index <23 kg/m², 23-24.9 kg/m², ≥25 kg/m²), MetS, each component of MetS, MetS stratified by obesity status, combination of obesity and MetS, and endometrial cancer risk were investigated using hazard ratios (HRs).ResultsObesity, each component of MetS, and MetS increased the endometrial cancer risk. After these factors were mutually adjusted for, the association did not change. When stratified by obesity, MetS and MetS components were not associated with endometrial cancer in normal-weight or overweight women. However, in obese women, MetS and MetS components increased the risk of endometrial cancer (HR=1.29; 95% confidence interval [CI]=1.20-1.39). Compared with normal-weight women without MetS, endometrial cancer risk was not increased in normal-weight women with MetS. Overweight women showed an increased risk of endometrial cancer irrespective of the presence of MetS (HR=1.37 and 1.38, respectively). The HR of obese women with MetS was higher than that of obese women without MetS (HR=2.18 and 1.75).ConclusionThe association between MetS and endometrial cancer was most prominent in obese women, suggesting that obese women with MetS would be more vulnerable to endometrial cancer.
| S-EPMC9250850 | biostudies-literature
Project description:PurposeTo investigate the association between metabolic syndrome (MetS) and risk of breast cancer mortality by menopausal status, obesity, and subtype.MethodsData from 94,555 women free of cancer at baseline in the National Institute of Health-American Association of Retired Persons Diet and Health Study cohort (NIH-AARP) were used to investigate the prospective associations of baseline MetS and components with risk of breast cancer mortality using Cox proportional hazard regression models adjusted for baseline behavioral and demographic covariates.ResultsDuring a mean follow-up duration of 14 years, 607 women in the cohort died of breast cancer. Overall, MetS was associated with a 73% increased risk of breast cancer mortality (HR 1.73; 95% CI 1.09-2.75); the association remained significant among post-menopausal women overall (HR 2.07, 95% CI 1.32, 3.25), and among those with overweight/obesity (HR 1.15, 95% CI 0.81, 1.64). MetS was associated with increased risk of breast cancer mortality for ER+/PR+ (HR 1.28, 95% CI 0.52, 3.16) and lower risk for ER-/PR- (HR 0.44, 95% CI 0.11, 1.75) subtypes; however, the associations were not statistically significant. Of the individual MetS components, high waist circumference (HR 1.32, 95% CI 1.03, 1.70), high cholesterol (HR 1.24, 95% CI 1.05, 1.46), and hypertension (HR 1.24, 95% CI 1.05, 1.46) were independently associated with increased risk of breast cancer mortality.ConclusionsMetS was associated with increased risk of breast cancer mortality, especially among post-menopausal women. Further studies with larger sample sizes are needed to definitively determine the extent to which these associations vary by breast cancer subtype.
| S-EPMC6461393 | biostudies-literature
Project description:BackgroundObesity and metabolic syndrome (MetS) are known to expose to atrial fibrillation (AF), cardiovascular diseases (CVD) and mortality. Metabolically healthy obesity refers to obesity without MetS. This study aimed to investigate how obesity and MetS modify the risk of CVD, AF and mortality in very long-time follow-up.MethodsFinnish middle-aged subjects (n = 1045) were grouped into four subgroups according to the presence of obesity and MetS. CVD events and AF were followed for 24 years and total mortality for 30 years. Moreover, 600 available patients had a follow-up visit for metabolic examinations after approximately 22 years.ResultsOne-hundred and sixty-two (30%) subjects without obesity or MetS died during the follow-up. Ninety-two (17%) of the patients in this group had a CVD event and 58 (11%) were diagnosed with AF. As compared to them, obese subjects without MetS had similar metabolic fate and mortality (mortality 26 (38%), p = .143; CVD event 12 (18%), p = .858 and AF 7 (10%), p = .912, respectively), whereas subjects with obesity and MetS had greater mortality (102 (49%), p < .001), more CVD (71 (34%), p < .001) and AF (49 (23%), p < .001). Non-obese individuals with MetS had greater rates of mortality (96 (44%), p < .001) and CVD (80 (37%), p < .001), but not of AF (26 (12%), p = .606). Of the 40 subjects with obesity but without MetS at baseline and available for the follow-up visit, 15 (38%) were metabolically healthy at the follow-up visit.ConclusionsIn the present long-term follow-up study, the presence of MetS, but not obesity only, implies a greater risk of mortality and CVD. The risk of AF is increased only in subjects with both obesity and MetS. However, obesity without MetS tends to progress eventually to obesity with MetS. Key messagesThe presence of metabolic syndrome (MetS), but not obesity only, entails a greater risk of mortality and cardiovascular diseases.The risk of atrial fibrillation is increased only in subjects with both obesity and MetS.Obesity without MetS tends to progress eventually to obesity with MetS.
| S-EPMC9132486 | biostudies-literature